Background Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial. Methods In this double-blind, parallel-group trial, 164 patients with stable cystic fibrosis who were at least six years old were randomly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent (control) saline twice daily for 48 weeks, with quinine sulfate (0.25 mg per milliliter) added to each solution to mask the taste. A bronchodilator was given before each dose, and other standard therapies were continued during the trial. Results The primary outcome measure, the rate of change (slope) in lung function (reflected by the forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and forced expiratory flow at 25 to 75 percent of FVC [FEF25–75]) during the 48 weeks of treatment, did not differ significantly between groups (P=...

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A Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis

Background The risk of invasive pneumococcal disease among persons with asthma is unknown. Methods We conducted a nested case–control study to examine the association between asthma and invasive pneumococcal disease. The study population included persons 2 to 49 years of age who were enrolled in Tennessee's Medicaid program (TennCare) for more than one year during the study period (1995 through 2002) and who resided in counties participating in a prospective laboratory-based program of surveillance for invasive pneumococcal disease. For each subject with invasive pneumococcal disease, 10 age-matched controls without invasive pneumococcal disease were randomly selected from the same population. TennCare files were queried to identify the presence of coexisting conditions that confer a high risk of pneumococcal disease. For the purpose of our study, asthma was defined by documentation of one or more inpatient or emergency-department diagnoses of asthma, two outpatient diagnoses, or the use of asthma-related...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa044113

Asthma as a Risk Factor for Invasive Pneumococcal Disease

Animal models of cystic fibrosis (CF) are powerful tools that enable the study of the mechanisms and complexities of human disease. Murine models have several intrinsic advantages compared with other animal models, including lower cost, maintenance, and rapid reproduction rate. Mice can be easily genetically manipulated by making transgenic or knockout mice, or by backcrossing to well-defined inbred strains in a reasonably short period of time. However, anatomic and immunologic differences between mice and humans mean that murine models have inherent limitations that must be considered when interpreting the results obtained from experimental models and applying these to the pathogenesis of CF disease in humans. This review will focus on the different CF mouse models available that represent diverse phenotypes observed in humans with CF and that can help researchers elucidate the diverse functions of the CFTR protein.

Cystic Fibrosis Mouse Models

http://www.stritch.luc.edu/lumen/MedEd/hostdef/CysticFibrosis.pdf

Innate immunity in cystic fibrosis lung disease

Background
Reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review.

Objectives
To assess the effectiveness of taking regular inhaled corticosteroids, compared to not taking them, in children and adults with cystic fibrosis.

Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.

Date of most recent search of the Group's Trials Register: 15 August 2016.

Selection criteria
Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.

Data collection and analysis
Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas.

Main results
The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 506 people with cystic fibrosis aged between six and 55 years. One was a withdrawal trial in individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information. Many of the risk of bias judgements were unclear due to a lack of available information. Only two trials specified how participants were randomised and less than half of the included trials gave details on how allocation was concealed. Trials were generally judged to have a low risk of bias from blinding, except for two which were open label or did not use a placebo. There were some concerns that a number of trials had not been published in peer-reviewed journals, but the risk of bias from this was unclear. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses.

Authors' conclusions
Evidence from these trials is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.

/pdf/inhaled-corticosteroids-for-cystic-fibrosis-3hql0yz2yo.pdf

Inhaled corticosteroids for cystic fibrosis.

Cystic fibrosis (CF) lung disease is characterized by chronic neutrophilic inflammation and infection. Effective management of airway inflammation could complement other therapies for the treatment of CF. Recent progress has been made in understanding the signaling pathways regulating inflammatory cytokines in the lung. Here we examine the mechanisms responsible for inflammation in the CF lung, and discuss potential therapeutic strategies targeting inflammation.

https://www.atsjournals.org/doi/pdf/10.1165/rcmb.2004-0124TR

Jim Hu

Papers

Lung Inflammation as a Therapeutic Target in Cystic Fibrosis